A Study of Lebrikizumab in Adolescent Participants With Uncontrolled Asthma Who Are on Inhaled Corticosteroids and a Second Controller Medication

A Phase III, Randomized, Double-Blind, Placebo-Controlled Study to Assess the Efficacy, Safety, and Tolerability of Lebrikizumab in Adolescent Patients With Uncontrolled Asthma Who Are On Inhaled Corticosteroids and a Second Controller Medication.

This randomized, multicenter, double-blind, placebo-controlled, parallel-group study will evaluate the efficacy, safety, and tolerability of lebrikizumab in adolescent participants with asthma whose disease remains uncontrolled despite daily treatment with inhaled corticosteroids (ICS) therapy and at least one second controller medication. Participants will be randomized in a 1:1:1 ratio to receive double-blind treatment with either lebrikizumab ('High' or 'Low') or placebo, administered as subcutaneous (SC) every 4 weeks (Q4W) for 52 weeks, in addition to their standard-of-care therapy. This will be followed by an optional 52-week double-blind active-treatment extension. The anticipated time on study treatment is up to 104 weeks. Participants who complete the study to Week 104, discontinue prematurely or decide not to take part in the optional active-treatment extension will transition to the 20-week safety follow-up period.

Study Overview

• Status: Terminated
• Conditions: Asthma
• Intervention / Treatment: Drug: Lebrikizumab; Drug: Standard of Care; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 346
• Phase: Phase 3

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires, Argentina, C1425BEN
    • INAER
  • Mendoza, Argentina, M5500GFA
    • Instituto Respirar
  • San Miguel de Tucumán, Argentina, T4000CHE
    • Centro Integral de Medicina Respiratoria (CIMER)
  • San Miguel de Tucumán, Argentina, T4000IAR
    • Investigaciones en Patologías Respiratorias
  • Santa Fe, Argentina, S3000ASF
    • Instituto Del Buen Aire
  • Vicente López, Argentina, B1602DQD
    • CEMER Centro Medico de Enfermedades Respiratorias
• Brazil
  • Estado de Bahia
    • Salvador, Estado de Bahia, Brazil, 41940-455
      • Centro de Referencia em Enfermidades Respiratorias e Alergia - CEAR
  • Rio Grande do Sul
    • Porto Alegre, Rio Grande do Sul, Brazil, 90020-090
      • Santa Casa de Misericordia de Porto Alegre
    • Porto Alegre, Rio Grande do Sul, Brazil, 90610-000
      • Hospital Sao Lucas - PUCRS
  • São Paulo
    • Santo André, São Paulo, Brazil, 09060-650
      • Faculdade de Medicina do ABC - FMABC
    • Santo André, São Paulo, Brazil, 09080-000
      • Pesquisare Saúde Sociedade Simples
    • Sorocaba, São Paulo, Brazil, 18040-425
      • CMPC/Clinica de Alergia Martti Antila
    • São Paulo, São Paulo, Brazil, 05437-010
      • Instituto de Pesquisa Clínica e Medicina Avançada Ltda
• Canada
  • Ontario
    • London, Ontario, Canada, N6A 5B8
      • Private Practice - Dr. Brian D. Lyttle
• Colombia
  • Bogotá, Colombia
    • Hospital Santa Clara
• Czechia
  • Jihlava, Czechia, 586 01
    • Hofstetr Alois MUDr. s.r.o.
  • Teplice, Czechia, 415 01
    • Alergologie Teplice, s.r.o.
• France
  • Rouen, France, 76031
    • Hopital Charles Nicolle; cic
• Germany
  • Frankfurt, Germany, 60528
    • Universitaetsklinikum Frankfurt
  • Hamm, Germany, 59063
    • Evangelisches Krankenhaus Hamm
• Hungary
  • Budapest, Hungary, 1089
    • Heim Pál Gyermekkórház
  • Budapest, Hungary, 1088
    • Semmelweis Egyetem; Belgyogyaszati es Hematologiai Klinika
  • Debrecen, Hungary, 4031
    • Kenezy Korhaz Rendelointezet
  • Szeged, Hungary, 6720
    • Szegedi Tudomanyegyetem Szent-Gyorgyi Albert Klinikai Kozpont
  • Szigetvár, Hungary, 7900
    • Papp és Társa Bt.
• Israel
  • Haifa, Israel, 3109600
    • Rambam Health Care Campus
  • Jerusalem, Israel, 9103102
    • Shaare Zedek Medical Center
  • Petah Tikva, Israel, 49100
    • Schneider Children's Medical Center
  • Ramat Gan, Israel, 5265601
    • Chaim Sheba Medical Center
• Italy
  • Lombardy
    • Pavia, Lombardy, Italy, 27100
      • Fondazione IRCCS Policlinico San Matteo
• Mexico
  • Villahermosa, Mexico, 86035
    • Consultorio Especialidad Alergologia Pediatrica
  • Jalisco
    • Guadalajara, Jalisco, Mexico, 44130
      • Centro de Investigacion Medico Biologico y Terapia Avanzada, S.C.
    • Santa Cecilia, Jalisco, Mexico, 44700
      • Instituto Jalisciense de Investigacion Clinica S.A. de C.V.
  • Mexico CITY (federal District)
    • DF, Mexico CITY (federal District), Mexico
      • Grupo Medico Camino
  • Nuevo León
    • Monterrey, Nuevo León, Mexico, 64718
      • Unidad de Investigacion Clinica En Medicina (Udicem) S.C.
• Peru
  • Lima, Peru, Lima 1
    • Clinica Internacional
  • Lima, Peru, LIMA 27
    • Centro de Investigación Ricardo Palma
• Poland
  • Krakow, Poland, 30-727
    • Malopolskie Centrum Alergologii
  • Lodz, Poland, 93-513
    • Wojewodzkie Wielospecjalistyczne Centrum Onkologii i Traumatologii im. M. Kopernika w Lodzi
  • Lodz, Poland, 90-153
    • SPZOZ Uniwersytecki Szpital Kliniczny nr 1 im. Norberta Barlickiego Uniwersytetu Medycznego w Lodzi
  • Poznan, Poland, 60-214
    • Centrum Alergologii Teresa Hofman
  • Tarnów, Poland, 33-100
    • ALERGO-MED Specjalistyczna Przychodnia Lekarska Sp. z o. o
  • Warsaw, Poland, 02-507
    • Klinika Chorób Wewnetrznych i Alergologii MSW
• Portugal
  • Aveiro, Portugal, 3814-501
    • Hospital Infante D. Pedro; Servico de Imunoalergologia
  • Faro, Portugal, 8005-226
    • Hospital Particular do Algarve - Unidade de Faro
  • Senhora Da Hora - Porto, Portugal, 4460-188
    • Hospital CUF Porto; Servico de Imunoalergologia
• Slovakia
  • Nitra, Slovakia, 949 01
    • Imunoalergologia Dzurilla s.r.o.
• South Africa
  • Cape Town, South Africa, 7925
    • Uni of Cape Town Lung Inst.
  • Durban, South Africa, 4001
    • Sebastian Peter
  • Johannesburg, South Africa, 1501
    • WWCT Lakeview Hospital
  • Pretoria, South Africa, 0101
    • Bothe ke Bontle Health Services
  • Soweto, South Africa, 1818
    • Soweto Clinical Trial Centre
• Spain
  • Barcelona
    • Badalona, Barcelona, Spain, 08916
      • Hospital Universitario Germans Trias i Pujol; Servicio de Farmacia
    • Sabadell, Barcelona, Spain, 8208
      • Corporacio Sanitaria Parc Tauli; Servicio de Oncologia
  • Valencia
    • Manises, Valencia, Spain, 46940
      • Hospital de Manises
• Taiwan
  • Tainan, Taiwan, 00704
    • National Cheng Kung Univ Hosp
• Ukraine
  • Chernivtsi, Ukraine, 58023
    • Municipal Medical Institution; Chernivtsi Regional Children's Hospital
  • Dnipro, Ukraine, 49000
    • Public Institution City Clinical Hospital # 6 of Dnipropetrovsk Regional Board
  • Kiev, Ukraine, 04050
    • State Institution of Pediatrics Obstetrics and Gynecology of NAMSU
  • Kryvyi Rih, Ukraine, 50082
    • Municipal Institution "Kryvyi Rih City Clinical Hospital #8" of Dnipropetrovsk Regional Council
  • Kyiv, Ukraine, 03680
    • SI National Institute of Phthisiology and Pulmonology n.a. F.G.Yanovskyi under NAMS of Ukraine
  • Kyiv, Ukraine, 3115
    • SI Research Centre of Radiation Medicine of AMSU
  • Zaporizhzhya, Ukraine, 69063
    • Municipal Institution Zaporizhzhya Regional Clinical Child Hospital
• United Kingdom
  • Birmingham, United Kingdom, B9 5SS
    • Birmingham Heartlands Hospital
  • Leicester, United Kingdom, LE1 7RH
    • University of Leicester
• United States
  • California
    • Mission Viejo, California, United States, 92691
      • Southern California Research Center
    • Stockton, California, United States, 95207
      • Bensch Research Associates
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Colorado Children's Hospital; The Breathing Institute
    • Centennial, Colorado, United States, 80112
      • IMMUNOe Research Centers
    • Colorado Springs, Colorado, United States, 80907
      • Asthma & Allergy; Associates, P.C.
  • Florida
    • Miami, Florida, United States, 33165
      • Abel and Buchheim
    • Sarasota, Florida, United States, 34239
      • Sarasota Clinical Research
  • Georgia
    • Marietta, Georgia, United States
      • Georgia Pain Clinic
  • Illinois
    • Chicago, Illinois, United States, 60612
      • Rush University Medical Center
  • Maryland
    • Baltimore, Maryland, United States, 21236
      • Asthma, Allergy & Sinus Center
  • New York
    • The Bronx, New York, United States, 10459
      • Urban Health Plan, Inc.
  • Texas
    • Boerne, Texas, United States, 78006
      • TTS Research
    • San Antonio, Texas, United States, 78251
      • Allergy & Asthma Res Ctr PA
    • San Antonio, Texas, United States, 78251
      • South Texas Allergy and Asthma Medical Professionals
  • Utah
    • North Logan, Utah, United States, 84341
      • Bridgerland Clinical Research
  • Virginia
    • Fairfax, Virginia, United States, 22030
      • O & O Alpan, LLC

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years to 17 years (Child)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Asthma diagnosis for greater than or equal to (>/=) 12 months prior to Visit 1
• Bronchodilator response during screening
• Pre-bronchodilator FEV1 of 40 percent (%) - 90% predicted at both Visits 2 and 3
• On high dose ICS therapy for >/= 6 months prior to Visit 1
• On an eligible second controller medication for 6 months prior to Visit 1
• Uncontrolled asthma as defined by the protocol both during screening and at the time of randomization
• Demonstrated adherence with controller medication during the screening period

Exclusion Criteria:

• History of severe allergic reaction or anaphylactic reaction to a biologic agent or known hypersensitivity to any component of the lebrikizumab injection
• Maintenance oral corticosteroid therapy within 3 months prior to Visit 1
• Treatment with systemic (oral, intravenous [IV], or intramuscular [IM]) corticosteroids within 4 weeks prior to Visit 1 or during the screening period
• Treatment with intra-articular corticosteroids within 4 weeks prior to Visit 1 or during the screening period or anticipated need for intra-articular corticosteroids during the course of the study
• Infection that meets the following criteria: Any infection requiring hospital admission or requiring treatment with IV or IM antibiotics within 4 weeks prior to Visit 1 or during screening; any active infection that required treatment with oral antibiotics within 2 weeks prior to Visit 1 or during screening; upper or lower respiratory tract infection within 4 weeks prior to Visit 1 or during screening; active parasitic infection or Listeria monocytogenes infection within 6 months prior to Visit 1 or during screening
• History of active tuberculosis requiring treatment
• Known immunodeficiency, including, but not limited to, human immunodeficiency virus (HIV) infection
• Evidence of acute or chronic hepatitis or known liver cirrhosis
• History of cystic fibrosis, bronchiectasis, and/or other clinically significant lung disease other than asthma
• Diagnosis or history of malignancy or current evaluation for potential malignancy
• Current smoker or former smoker with a history of greater than (>) 10 pack-years
• History of alcohol or drug abuse
• Past and/or current use of any anti- interleukin (IL) -13 or anti-IL-4/IL-13 therapy, including lebrikizumab
• Use of other monoclonal antibody therapy, including omalizumab, within 6 months or 5 drug half-lives (whichever is longer) prior to Visit 1
• Initiation of or change in allergen immunotherapy within 3 months prior to Visit 1 or during screening
• History of bronchial thermoplasty

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Lebrikizumab High; Participants with uncontrolled asthma on ICS therapy (total daily dose of 500-2000 micrograms [mcg] of fluticasone propionate dry powder inhaler [DPI] or equivalent) and a second controller medication, will receive SC injection of lebrikizumab (high dose) Q4W for 52 weeks during placebo-controlled period and up to 76 weeks or 104 weeks for participants who will be willing to take part in optional active-treatment extension period.	Drug: Lebrikizumab; Lebrikizumab will be administered as SC injection at high or low dose Q4W.; Drug: Standard of Care; Participants will continue to receive ICS therapy (total daily dose of 500-2000 mcg fluticasone propionate DPI or equivalent) along with at least one second controller medications (e.g. long-acting beta agonists [LABAs], leukotriene receptor antagonists (LTRAs), long-acting muscarinic antagonists (LAMAs), or theophylline) as standard of care.
Experimental: Lebrikizumab Low; Participants with uncontrolled asthma on ICS therapy (total daily dose of 500-2000 mcg of fluticasone propionate DPI or equivalent) and a second controller medication, will receive SC injection of lebrikizumab (low dose) Q4W for 52 weeks during placebo-controlled period and up to 76 weeks or 104 weeks for participants who will be willing to take part in optional active-treatment extension period.	Drug: Lebrikizumab; Lebrikizumab will be administered as SC injection at high or low dose Q4W.; Drug: Standard of Care; Participants will continue to receive ICS therapy (total daily dose of 500-2000 mcg fluticasone propionate DPI or equivalent) along with at least one second controller medications (e.g. long-acting beta agonists [LABAs], leukotriene receptor antagonists (LTRAs), long-acting muscarinic antagonists (LAMAs), or theophylline) as standard of care.
Placebo Comparator: Placebo; Participants with uncontrolled asthma on ICS therapy (total daily dose of 500-2000 mcg of fluticasone propionate DPI or equivalent) and a second controller medication, will receive SC injection of lebrikizumab matching placebo Q4W for 52 weeks during placebo-controlled period and then SC injection of lebrikizumab at high or low dose will be administered from Weeks 52 to 76 or 104 to participants who are willing to take part in optional active-treatment extension period.	Drug: Lebrikizumab; Lebrikizumab will be administered as SC injection at high or low dose Q4W.; Drug: Standard of Care; Participants will continue to receive ICS therapy (total daily dose of 500-2000 mcg fluticasone propionate DPI or equivalent) along with at least one second controller medications (e.g. long-acting beta agonists [LABAs], leukotriene receptor antagonists (LTRAs), long-acting muscarinic antagonists (LAMAs), or theophylline) as standard of care.; Drug: Placebo; Lebrikizumab matching placebo will be administered as SC injection Q4W.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of Asthma Exacerbations During 52-Week Placebo Controlled Period	An asthma exacerbation is defined as new or increased asthma symptoms (including wheeze, cough, dyspnea, chest tightness, and/or night-time awakening due to these symptoms) that lead to treatment with systemic corticosteroids or to hospitalization. Treatment with systemic corticosteroids is defined as treatment with oral, intravenous (IV), or intramuscular (IM) corticosteroids for at least 3 days or an emergency department visit with at least 1 dose of IV or IM corticosteroids. Rate of asthma exacerbation = total number of exacerbation events divided by total follow-up time in patient years.	Baseline up to Week 52

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent Change From Baseline in Pre-Bronchodilator Forced Expiratory Volume in 1 Second (FEV1) at Week 52	FEV1 is the maximal volume of air exhaled in the first second of a forced expiration from a position of full inspiration. The baseline FEV1 was obtained from the last spirometric analysis performed before the first study treatment administration. The percentage change in pre-bronchodilator FEV1 was defined as the change in FEV1 (in liters) from baseline divided by the FEV1 (in liters) at baseline multiplied by 100.	Week 52
Absolute Change From Baseline in Pre-Bronchodilator FEV1 at Week 52	FEV1 is the maximal volume of air exhaled in the first second of a forced expiration from a position of full inspiration. The baseline FEV1 was obtained from the last spirometric analysis performed before the first study treatment administration. Reported is the absolute change from baseline in FEV1 to the end of the placebo-controlled period at Week 52.	Week 52
Time to First Asthma Exacerbation	An asthma exacerbation was defined as new or increased asthma symptoms (including wheeze, cough, dyspnea, chest tightness, and/or night-time awakening due to these symptoms) that lead to treatment with systemic corticosteroids or to hospitalization. Treatment with systemic corticosteroids was defined as treatment with oral, IV, or IM corticosteroids for at least 3 days or an emergency department visit with at least 1 dose of IV or IM corticosteroids. Median time to first protocol-defined asthma exacerbation was estimated using Kaplan-Meier analysis. 95% Confidence interval (CI) for median was computed using the method of Brookmeyer and Crowley.	Baseline up to Week 52
Change From Baseline in Fractional Exhaled Nitric Oxide (FeNO) at Week 52	Measurement of FeNO (in parts per billion [ppb]) was performed using a hand-held portable NIOX MINO® device, in accordance with guidelines published by the American Thoracic Society (ATS) and described in the pulmonary function testing manual.	Week 52
Change From Baseline in Standardized Asthma Quality of Life Questionnaire for 12 Years and Older (AQLQ+12) Overall Score at Week 52	The Standardized AQLQ+12 was used to assess the participants' asthma-specific health-related quality of life. The AQLQ+12 had a recall specification of 2 weeks. The AQLQ+12 was a 32-item questionnaire with 4 domains: activity limitations, symptoms, emotional function, and environmental stimuli. Each of the 32 questions were scored on a scale 1-7. The overall AQLQ+12 score is the mean of the responses to each of the 32 questions, and ranges from 1 to 7. A score 7 indicated no impairments due to asthma, and a score of 1 indicated severe impairment.	Week 52
Change From Baseline in Asthma Rescue Medication Use at Week 52	Participants were allowed to use short-acting bronchodilators as asthma rescue medication. Baseline asthma rescue medication use was defined as the average number of puffs per day over the 7 days prior to and on the day of randomization. Participants must have recorded their asthma rescue medication use for at least 4 days to have a baseline score calculated. The post-baseline asthma medication use for any timepoint was defined as the average number of puffs per day over the last 28 days on or prior to the timepoint. Participants must have recorded their asthma rescue medication use for at least 14 days during a 28-day interval to have a score calculated for the respective timepoint. For nebulizer use, one treatment (inhalation) was considered equivalent to 4 puffs.	Week 52
Rate of Urgent Asthma-Related Health Care Utilization (HCU) Events	Urgent asthma-related HCU events included hospitalizations, emergency department visits, and acute care visits. Rate of urgent asthma-related HCU events = total number of urgent asthma-related HCU events divided by total follow-up time in patient years.	Baseline up to Week 52
Injection Acceptability Questionnaire (IAQ) Score	The acceptability of the injections of study drug was addressed by measuring the level of pain that participants experienced. Participants assessed pain associated with study drug administration using the IAQ within 10 minutes of study drug administration. The IAQ score ranged from 0 to 10; where 0 = no pain and 10 = worst pain imaginable.	Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48
Minimum Observed Serum Concentration (Ctrough) for Lebrikizumab	Participants who received at least one dose of lebrikizumab and had at least one post-baseline evaluable sample were included in the analysis. Results of post-dose samples which were less than reportable were set to 0.045 micrograms per milliliter (mcg/mL) that is half of minimum quantifiable concentration value (0.09 mcg/mL).	Predose (Hour 0) at Weeks 4, 12, 24, 36, and 52

Collaborators and Investigators

• Sponsor: Hoffmann-La Roche
• Investigators: Study Director: Clinical Trials, Hoffmann-La Roche

Publications and helpful links

General Publications

• Szefler SJ, Roberts G, Rubin AS, Zielen S, Kuna P, Alpan O, Anzures-Cabrera J, Chen Q, Holweg CTJ, Kaminski J, Putnam WS, Matthews JG, Kamath N. Efficacy, safety, and tolerability of lebrikizumab in adolescent patients with uncontrolled asthma (ACOUSTICS). Clin Transl Allergy. 2022 Jul 14;12(7):e12176. doi: 10.1002/clt2.12176. eCollection 2022 Jul.

Study record dates

Study Major Dates

• Study Start (Actual): August 13, 2013
• Primary Completion (Actual): December 28, 2016
• Study Completion (Actual): December 28, 2016

Study Registration Dates

• First Submitted: June 7, 2013
• First Submitted That Met QC Criteria: June 7, 2013
• First Posted (Estimated): June 11, 2013

Study Record Updates

• Last Update Posted (Actual): June 30, 2026
• Last Update Submitted That Met QC Criteria: June 19, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Respiratory Tract Diseases; Lung Diseases; Bronchial Diseases; Lung Diseases, Obstructive; Respiratory Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Asthma; Health Services Administration; Health Care Quality, Access, and Evaluation; Quality of Health Care; Quality Indicators, Health Care; Standard of Care; lebrikizumab
• Other Study ID Numbers: WB28183; 2012-000180-25 (EudraCT Number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes